Cystic fibrosis (CF) is a genetic disease resulting from a variety of defects of the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is involved in the transport of chloride and bicarbonate ions across the cell membrane. CF mostly affects the lungs, intestines and pancreas. The progression of the CF disease is most commonly associated with decline in pulmonary function; however, the CFTR also affects electrolyte transport in many organs including the GI tract, resulting in pancreatic insufficiency, nutritional malabsorption, and significant reductions in gastrointestinal (GI) motility, altering te fecal microbiota. In the GI tract, the reduction or loss of CFTR function results in abnormal electrolyte composition and dehydration of the lumen, resulting in thick adherent mucus and reduced GI motility, as also observed in the lungs. Consequently, meconium ileus is observed in 13-17% of CF newborns and causes significant morbidity, including large resections of bowel that cause permanent disability. Distal intestinal obstructive syndrome (DIOS), formerly called meconium ileus (MI) equivalent, causes similar events in older children and adults, and is associated with severe morbidity and prolonged hospitalizations. Current treatments are non-specific and similar to that used for the non-CF population, but with greatly increased intensity; this includes osmotic stool softeners and supplementation with stimulant laxatives but do not address the underlying cause of mucus and stool obstruction. Currently, no current treatments are intended to address the underlying adhesive properties of CF mucus that cause impacted mucus, stool and associated inflammation, representing a significant unmet medical need. This proposal tests a novel, orally administered polysaccharide therapeutic with demonstrated pulmonary mucolytic activity and anti- inflammatory GI action, to treat CF obstructive disorders and associated intrinsic inflammation. Both prophylaxis and treatment of GI obstruction will be tested in rat models. Biomarkers of inflammation and GI damage will be assessed along with gene expression changes in the ileum and jejunum associated with treatment in order to better understand mechanisms of action. This proof of principle study will be used to determine the efficacy of this new therapeutic and its potential for advancement as a drug candidate.